Granted Patent
B2
US 12,350,303 · App. 16/482,623 · Granted Jul 8, 2025
Oncolytic virus therapy
Inventors:
Zong Sheng Guo (Wexford, PA); David Bartlett (Pittsburgh, PA); Zuqiang Liu (Wexford, PA); Mathilde Feist (Pittsburgh, PA)
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Abstract
The presently disclosed subject matter relates to tumor infiltrated T cells induced by oncolytic virus (“OV-induced T cells”), methods of making and using said OV-induced T cells for an adoptive T-cell therapy. The presently disclosed subject matter further relates to oncolytic viruses and armed oncolytic viruses, methods of making and using said oncolytic viruses, as well as pharmaceutical compositions and kits comprising said oncolytic viruses.
Claims (9)
1. An oncolytic virus comprising, in its genome, a nucleic acid encoding a membrane-associated fusion protein comprising an immunomodulator molecule directly linked to an anchoring peptide via a rigid linker, wherein:
the immunomodulator molecule comprises SEQ ID NO: 13 or SEQ ID NO: 13 with one or two amino acid variations;
the oncolytic virus is a vaccinia virus;
the nucleic acid is operably linked to an oncolytic virus promoter;
the rigid linker is a peptide linker between 1 and 25 amino acids in length; and
the anchoring peptide comprises a GPI-anchor acceptor peptide.
2. The oncolytic virus of claim 1 , wherein said rigid linker comprises SEQ ID NO:36.
3. The oncolytic virus of claim 1 , wherein the oncolytic virus is a recombinant vaccinia virus with an inactivating mutation of its thymidine kinase gene, vaccinia growth factor gene, or both.
4. The oncolytic virus of claim 1 , wherein said GPI-anchor acceptor peptide comprises SEQ ID NO: 11.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 27, 2020
From: GUO, ZONG SHENG; BARTLETT, DAVID; LIU, ZUQIANG; FEIST, MATHILDE
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 053895/0308 →
Continuity (2)
Provisional Application
62454526
· Feb 3, 2017
References Cited (186)
US 6277368B1
· Hiserodt et al.
· 2001
[cited by applicant]
US 7208313B2
· McCart et al.
· 2007
[cited by applicant]
US 7264820B2
· Hiserodt et al.
· 2007
[cited by applicant]
US 8506947B2
· McCart et al.
· 2013
[cited by applicant]
US 20030105054A1
· Wagner
· 2003
[cited by examiner]
US 20030170238A1
· Gruenberg et al.
· 2003
[cited by applicant]
US 20100303714A1
· Kirn
· 2010
[cited by applicant]
US 20150250837A1
· Nolin
· 2015
[cited by examiner]
US 20160000842A1
· Song et al.
· 2016
[cited by applicant]
US 20170291934A1
· Reed et al.
· 2017
[cited by applicant]
US 20230002465A1
· Bartlett
· 2023
[cited by examiner]
CA 2962099
· 2016
[cited by applicant]
CN 101912421
· 2010
[cited by applicant]
CN 105658795
· 2016
[cited by applicant]
CN 110267978
· 2019
[cited by applicant]
JP 2009507853
· 2009
[cited by applicant]
JP 2016512199
· 2016
[cited by applicant]
JP 2016527920
· 2016
[cited by applicant]
WO WO1999006544
· 1999
[cited by applicant]
WO WO2003017944
· 2003
[cited by applicant]
WO WO2008113078
· 2008
[cited by applicant]
WO WO2012142529
· 2012
[cited by applicant]
WO WO2014138314
· 2014
[cited by applicant]
WO WO2015027163
· 2015
[cited by applicant]
WO WO2016174200
· 2016
[cited by applicant]
WO WO2016070136
· 2016
[cited by applicant]
WO WO2016146894
· 2016
[cited by applicant]
WO WO2017044780
· 2017
[cited by applicant]
WO WO2017165464
· 2017
[cited by applicant]
WO WO2017201350
· 2017
[cited by applicant]
WO WO2018145033
· 2018
[cited by applicant]
WO WO2018213731
· 2018
[cited by applicant]
WO WO2020124274
· 2020
[cited by applicant]
U.S. Appl. No. 17/778,463 filed May 2022, Bartlett, David.
[cited by examiner]
UniProt Accession No. O75015, 9 pages (first available 1999) (Year: 1999).
[cited by examiner]
“Anchor”, The Free Dictionary, available online at www.thefreedictionary.com/anchoring, 6 pages (accessed on Nov. 1, 2022) (Year: 2022).
[cited by examiner]
Arai et al., Prot. Eng. 14:529-532 (2001) (Year: 2001).
[cited by examiner]
GenBank Accession No. CAA25742.1 (2008) (Year: 2008).
[cited by examiner]
Epstein et al., J. Natl. Cancer Inst. 95:741-749 (2003) (Year: 2003).
[cited by examiner]
Medof et al., FASEB J. 10:574-586 (1996) (Year: 1996).
[cited by examiner]
NCBI Database, GenBank Accession No. AAH66254.1, 2 pages (2007) (Year: 2007).
[cited by examiner]
Kaufman et al., Nat. Rev. 14:642-662 (2015) (Year: 2015).
[cited by examiner]
EPFL, “Designing Linkers: A comprehensive guide by the EPFL 2021 iGEM team,” available online at https://static.igem.org/mediawiki/2021/d/de/T--EPFL--contribution--linkers.pdf, 6 pages (2021) (Year: 2021).
[cited by examiner]
Chen et al., Adv. Drug Deliv. Rev. 65:1357-1369 (2013) (Year: 2013).
[cited by examiner]
Vagner et al., Bioconjug. Chem. 17:1545-1550 (2006) (Year: 2006).
[cited by examiner]
Alvarez-Breckenridge et al., “NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors,” Nat Med., 2012, 18(12):1827-1834.
[cited by applicant]
Andtbacka et al., “Talimogene laherparepvec improves durable response rate in patients with advanced melanoma,” J clin Oncol., Sep. 2015, 33(25):2780-8.
[cited by applicant]
Baluna and Vitetta, “Vascular leak syndrome: a side effect of immunotherapy,” Immunopharmacology, Oct. 1997, 37(2-3):117-32.
[cited by applicant]
Bartlett et al., “Oncolytic viruses as therapeutic cancer vaccines,” Molecular cancer, 2013 Dec. 2013, 12(1):103.
[cited by applicant]
Bourgeois-Daigneault et al., “Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy,” Science Translational Medicine, Jan. 2018, 10(422):eaao1641.
[cited by applicant]
Boyman and Sprent, “The role of interleukin-2 during homeostasis and activation of the immune system,” Nature Reviews Immunology, Mar. 2012, 12(3):180-90.
[cited by applicant]
Boyman et al., “Potential use of IL-2/anti-IL-2 antibody immune complexes for the treatment of cancer and autoimmune disease,” Expert opinion on biological therapy, Dec. 2006, 6(12):1323-31.
[cited by applicant]
Boyman et al., “Selective stimulation of T cell subsets with antibody-cytokine immune complexes,” Science, Mar. 2006, 311(5769):1924-7.
[cited by applicant]
Brandacher et al., “Prognostic value of indoleamine 2, 3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells,” Clinical cancer research, Feb. 2006, 12(4):1144-51.
[cited by applicant]
Chatterjee et al., “The intricate role of CXCR4 in cancer,” InAdvances in cancer research, Academic Press, Jan. 2014, 124:31-82.
[cited by applicant]
Chiocca and Rabkin, “Oncolytic viruses and their application to cancer immunotherapy,” [published correction appears in Cancer Immunol Res. Jul. 2014;2(7):699], Cancer Immunol Res., 2014, 2(4):295-300.
[cited by applicant]
Dennis et al., Current status of IL-10 and regulatory T-cells in cancer, Current opinion in oncology, Nov. 2013, 25(6):637.
[cited by applicant]
Downs-Canner et al., “Phase 1 study of intravenous oncolytic poxvirus (vvDD) in patients with advanced solid cancers,” Molecular Therapy, Aug. 2016, 24(8):1492-501.
[cited by applicant]
Feig et al., “Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer,” Proceedings of the National Academy of Sciences, 2013, 110(50):20212-20…
[cited by applicant]
Ferguson et al., “Chapter 11: Glycosylphosphatidyl Anchors” in Glycobiology, 2nd Edition, Varki et al., editors, Cold Spring Harbor Press, 2009 Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, …
[cited by applicant]
Fridman et al., “The immune contexture in human tumours: impact on clinical outcome,” Nature Reviews Cancer, Apr. 2012, 12(4):298-306.
[cited by applicant]
Fukunaga et al., “CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma,” Pancreas, Jan. 2004, 28(1):e…
[cited by applicant]
Galian et al., “Efficient glycosylphosphatidylinositol (GPI) modification of membrane proteins requires a C-terminal anchoring signal of marginal hydrophobicity,” Journal of Biological Chemistry, May 2012, 287(20):16399…
[cited by applicant]
Galon et al., “Type, density, and location of immune cells within human colorectal tumors predict clinical outcome,” Science, Sep. 2006, 313(5795):1960-4.
[cited by applicant]
Gao et al., “Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection,” Journal of clinical oncology, Jun. 2007, 25(18):2586-93.
[cited by applicant]
Gao et al., “Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma, ” Clin. Cancer Res., 2009, 15(3):971-979.
[cited by applicant]
GenBank Accession No. CAA25742.1, “human interleukin 2 [
[cited by applicant]
GenBank Accession No. NM_000594.3, “
[cited by applicant]
Guo et al., “Oncolytic immunotherapy: conceptual evolution, current strategies, and future perspectives,” Frontiers in immunology, May 2017, 8:555.
[cited by applicant]
Guo et al., “Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity,” Frontiers in oncology, Apr. 2014, 4:74.
[cited by applicant]
Guo et al., “Oncolytic virotherapy: molecular targets in tumor-selective replication and carrier cell-mediated delivery of oncolytic viruses,” Biochim Biophys Acta., 2008, 1785(2):217-231.
[cited by applicant]
Guo et al., “The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2,” Cancer Res., 2005 65(21):9991-9998.
[cited by applicant]
Heo et al., “Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer,” Nat Med., 2013, 19(3):329-336.
[cited by applicant]
Hu et al., “Generation of low-toxicity interleukin-2 fusion proteins devoid of vasopermeability activity,” Blood, Jun. 2003, 101(12):4853-61.
[cited by applicant]
International Preliminary Report on Patentability International Application No. PCT/US2018/016912 dated Aug. 6, 2019, 8 pages.
[cited by applicant]
International Search Report in International Application No. PCT/US2018/016912 dated May 10, 2018, 4 pages.
[cited by applicant]
Ji et al., “Glycoinositol Phospholipid-anchored Interleukin 2 but not Secreted Interleukin 2 Inhibits Melanoma Tumor Growth in Mice 1 Supported by the Oncology Research Endowment of the Greenville Hospital System,” Mole…
[cited by applicant]
Katre et al., “Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model,” Proceedings of the national academy of sciences, Mar. 1987, 84(6):1487-…
[cited by applicant]
Kaufman et al., “Oncolytic viruses: a new class of immunotherapy drugs,” Nature reviews Drug discovery, Sep. 2015, 14(9):642-62.
[cited by applicant]
Kirn et al., “Enhancing poxvirus oncolytic effects through increased spread and immune evasion,” Cancer research, Apr. 2008, 68(7):2071-5.
[cited by applicant]
Kobayashi et al., “T1365 FOXP3+ Regulatory T Cells and Tumoral Indoleamine 2, 3-Dioxygenase Expression Predicts the Carcinogenesis of the Pancreas,” Gastroenterology, May 2010, 138(5):S-546.
[cited by applicant]
Kottke et al., “Subversion of NK-cell and TNFα immune surveillance drives tumor recurrence,” Cancer immunology research, Nov. 2017, 5(11):1029-45.
[cited by applicant]
Lazear et al., “Targeting of IL-2 to cytotoxic lymphocytes as an improved method of cytokine-driven immunotherapy,” Oncoimmunology, Feb. 2017, 6(2):e1265721.
[cited by applicant]
Lee et al., “Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer,” Br. J. Cancer, 2008, 99(10):1704-1711.
[cited by applicant]
Lentsch et al., “Interleukin-10 inhibits interleukin-2-induced tumor necrosis factor production but does not reduce toxicity in C3H/HeN mice,” Journal of leukocyte biology, Jul. 1996, 60(1):51-7.
[cited by applicant]
Létourneau et al., “IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor a subunit CD25,” Proceedings of the National Academy of Sciences, Feb. 2010, 107(5):2171-6.
[cited by applicant]
Levin et al., “Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’,” Nature, Apr. 2012, 484(7395):529-33.
[cited by applicant]
Li et al., “Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer,” Molecular Therapy, Apr. 2011, 19(4):650-7.
[cited by applicant]
Liao et al., “Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy,” Immunity, Jan. 2013, 38(1):13-25.
[cited by applicant]
Liu et al., “CXCL11-Armed oncolytic poxvirus elicits potent antitumor immunity and shows enhanced therapeutic efficacy,” Oncoimmunology, Mar. 2016, 5(3):e1091554.
[cited by applicant]
Liu et al., “Isolation of mouse tumor-infiltrating leukocytes by Percoll gradient centrifugation,” Bio-Protocol., 2013, 3(17).
[cited by applicant]
Liu et al., “Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy,” Nature communications, Mar. 2017, 8(1):1-2.
[cited by applicant]
Lotze et al., “In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2,” J. Immunol., Oct. 1985, 135(4):2865-2…
[cited by applicant]
Martínez-Bosch et al., “Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation,” Cancer Res, 2014, 74(13):3512-3524.
[cited by applicant]
Matzinger, “The danger model: a renewed sense of self,” Science, Apr. 2002, 296(5566):301-5.
[cited by applicant]
Mayor and Riezman, “Sorting GPI-anchored proteins,” Nature reviews Molecular cell biology, Feb. 2004, 5(2):110-20.
[cited by applicant]
McCart et al., “Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes,” Cancer research, Dec. 2001, 61(24):8751-7.
[cited by applicant]
Medzhitov and Janeway, “Decoding the patterns of self and nonself by the innate immune system,” Science, Apr. 2002, 296(5566):298-300.
[cited by applicant]
Melder et al., “Pharmacokinetics and in vitro and in vivo anti-tumor response of an interleukin-2-human serum albumin fusion protein in mice,” Cancer immunology, immunotherapy, Jun. 2005, 54(6):535-47.
[cited by applicant]
Nakakubo et al., “Clinical significance of immune cell infiltration within gallbladder cancer,” British journal of cancer, Nov. 2003, 89(9):1736-42.
[cited by applicant]
Pagès et al., “Effector memory T cells, early metastasis, and survival in colorectal cancer,” New England journal of medicine, Dec. 2005, 353(25):2654-66.
[cited by applicant]
Pan et al., “Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains,” Molecular Therapy, May 2012, 20(5):927-37.
[cited by applicant]
Paulick and Bertozzi, “The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins,” Biochemistry, Jul. 2008, 47(27):6991-7000.
[cited by applicant]
Puskas et al., “Development of an Attenuated interleukin-2 Fusion Protein That Can Be Activated by Tumour-Expressed Proteases,” Immunology, Jun. 2011, 133(2):206-20.
[cited by applicant]
Qin et al., “Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression, ” Molecular Therapy, Dec. 2001, 4(6):551-8.
[cited by applicant]
Quandt et al., “B7-h4 expression in human melanoma: its association with patients' survival and antitumor immune response,” Clinical cancer research, May 2011, 17(10):3100-11.
[cited by applicant]
Ribas et al., “Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy,” Cell, Sep. 2017, 170(6):1109-19.
[cited by applicant]
Rintoul et al., “A selectable and excisable marker system for the rapid creation of recombinant poxviruses, ” PloS one, 2011, 6(9).
[cited by applicant]
Rosenstein et al., “Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2,” The Journal of Immunology, Sep. 1986, 137(5):1735-42.
[cited by applicant]
Russell et al., “Oncolytic virotherapy,” Nature biotechnology, Jul. 2012, 30(7):658.
[cited by applicant]
Saha et al., “Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade,” Cancer Cell, Aug. 2017, 32(2):253-67.
[cited by applicant]
Samson et al., “Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade,” Science translational medicine, Jan. 2018, 10(422):eaam 7577.
[cited by applicant]
Sathaiah et al., “Oncolytic poxvirus armed with Fas ligand leads to induction of cellular Fas receptor and selective viral replication in FasR-negative cancer,” Cancer gene therapy, Mar. 2012, 19(3):192-201.
[cited by applicant]
Siegal et al., “Cancer statistics,” Ca. cancer J. Clin., Jan. 2014, 64(1):9-29.
[cited by applicant]
Simmons and Seed, “The Fcγ receptor of natural killer cells is a phospholipid-linked membrane protein,” Nature, Jun. 1988, 333(6173):568-70.
[cited by applicant]
Takagi et al., “Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma,” Human pathology, Jul. 2004, 35(7):881-6.
[cited by applicant]
Tang et al., “PAMP s and DAMP s: signal Os that spur autophagy and immunity,” Immunological reviews, Sep. 2012, 249(1):158-75.
[cited by applicant]
Thorne et al., “Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963,” The Journal of clinical investigation, Nov. 2007, 117(11):3350-8.
[cited by applicant]
Vazquez-Lombardi et al., “Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells,” Nature communications, May 2017, 8(1):1-2.
[cited by applicant]
Written Opinion in International Application No. PCT/US2018/016912 dated May 10, 2018, 7 pages.
[cited by applicant]
Yang et al., “Randomized study of high-dose and low-dose inter leukin-2 in patients with metastatic renal cancer,” Journal of clinical oncology: official journal of the American Society of Clinical Oncology, Aug. 2003, …
[cited by applicant]
Zeh et al., “First-in-man study of western reserve strain oncolytic vaccinia virus: safety, systemic spread, and antitumor activity,” Molecular Therapy, Jan. 2015, 23(1):202-14.
[cited by applicant]
Zhang et al., “Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus,” Cancer research, Oct. 2007, 67(20):10038-46.
[cited by applicant]
Zou, “Immunosuppressive networks in the tumour environment and their therapeutic relevance,” Nature reviews cancer, Apr. 2005, 5(4):263-74.
[cited by applicant]
Feist et al., “Oncolytic virus promotes tumor-reactive infiltrating lymphocytes for adoptive cell therapy,” Cancer Gene Therapy, Jul. 7, 2020, 14 pages.
[cited by applicant]
Keller et al., “Oncolytic viruses-immunotherapeutics on the rise,” Journal of Molecular Medicine, Aug. 4, 2016, 94(9):979-991.
[cited by applicant]
Nguyen et al., “Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs),” PLOS One, Nov. 2010, 5(11):e13940, 12 pages.
[cited by applicant]
Poutou et al., “Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model,” Gene Therapy, May 21, 2015, 22(9):696-706.
[cited by applicant]
Rosenberg et al., “Adoptive cell transfer as personalized immunotherapy for human cancer,” Science, Apr. 3, 2015, 348(6230):62-68.
[cited by applicant]
Ge et al., “Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety,” J. Immunother. Cancer, Mar. 2020, 8(1):e000710, 8 pages.
[cited by applicant]
Abastado, “The next challenge in cancer immunotherapy: controlling T-cell traffic to the tumor,” Cancer Research, May 2012, 72(9):2159-2161.
[cited by applicant]
Abdi et al., “Free IL-12p40 Monomer Is a Polyfunctional Adaptor for Generating Novel IL-12-like Heterodimers Extracellularly,” J. Immunology, Jun. 15, 2014, 192(12):6028-6036.
[cited by applicant]
Atkins et al., “Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies,” Clin. Cancer Research, Mar. 1997, 3(3):409-417.
[cited by applicant]
Berraondo et al., “Revisiting Interleukin-12 as a Cancer Immunotherapy Agent,” Clin. Cancer Research, Jun. 15, 2018, 24(12):2716-2718.
[cited by applicant]
Bommareddy et al., “Integrating oncolytic viruses in combination cancer immunotherapy,” Nat. Rev. Immunology, Aug. 2018, 18(8):498-513.
[cited by applicant]
Brahmer et al., “Safety and activity of anti-PD-L1 antibody in patients with advanced cancer,” N. Engl. J. Medicine, Jun. 28, 2012, 366(26):2455-2465.
[cited by applicant]
Cao et al., “Interleukin 12 stimulates IFN-gamma-mediated inhibition of tumor-induced regulatory T-cell proliferation and enhances tumor clearance,” Cancer Research, Nov. 15, 2009, 69(22):8700-8709.
[cited by applicant]
Cervera-Carrascon et al., “TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade,” Oncoimmunology, Apr. 9, 2018, 7(5):e1412902, 12 pages.
[cited by applicant]
Chen et al., “Elements of cancer immunity and the cancer-immune set point,” Nature, Jan. 18, 2017, 541:321-330.
[cited by applicant]
Chen et al., “Oncology meets immunology: the cancer-immunity cycle,” Immunity, Jul. 25, 2013, 39(1):1-10.
[cited by applicant]
Chon et al., “Tumor Microenvironment Remodeling by Intratumoral Oncolytic Vaccinia Virus Enhances the Efficacy of Immune-Checkpoint Blockade,” Clin. Cancer Research, Mar. 1, 2019, 25(5):1612-1623.
[cited by applicant]
Cohen, “IL-12 deaths: explanation and a puzzle,” Science, Nov. 10, 1995, 270(5238):908.
[cited by applicant]
Colombo et al., “Interleukin-12 in anti-tumor immunity and immunotherapy,” Cytokine Growth Factor Reviews, Apr. 2002, 13(2):155-168.
[cited by applicant]
Efremova et al., “Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution,” Nat. Communications, Jan. 2, 2018, 9(1):32, 13 pages.
[cited by applicant]
Essentials of Glycobiology, 2nd ed., Varki et al. (eds.), 2009, Chapter 11, 27 pages.
[cited by applicant]
Extended European Search Report in European Appln. No. 20889840.3, dated Sep. 8, 2023, 12 pages.
[cited by applicant]
Fortin et al., “NK cell response to vaccinia virus is regulated by myeloid-derived suppressor cells,” J. Immunology, Aug. 15, 2012, 189(4):1843-1849.
[cited by applicant]
Gajewski, “The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment,” Semin. Oncology, Aug. 2015, 42(4):663-671.
[cited by applicant]
GenBank Accession No. BC128562.1, “
[cited by applicant]
Guo et al., “Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics,” J. Immunother. Cancer, Jan. 9, 2019, 7(1):6, 21 pages.
[cited by applicant]
Hodi et al., “Improved survival with ipilimumab in patients with metastatic melanoma,” N. Engl. J. Medicine, Aug. 19, 2010, 363(8): 711-723.
[cited by applicant]
Kowalsky et al., “Superagonist IL-15-Armed Oncolytic Virus Elicits Potent Antitumor Immunity and Therapy That Are Enhanced with PD-1 Blockade,” Mol. Therapy, Oct. 3, 2018, 26(10):2476-2486.
[cited by applicant]
Leach et al., “Enhancement of antitumor immunity by CTLA-4 blockade,” Science, Mar. 22, 1996, 271(5256):1734-1736.
[cited by applicant]
Leonard et al., “Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production,” Blood, Oct. 1, 1997, 90(7):2541-2548.
[cited by applicant]
Liu et al., “Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2,” Nat. Communications, Nov. 8, 2018, 9(1):4682, 9 pages.
[cited by applicant]
Mariathasan et al., “Tgfβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells, ” Nature, Feb. 22, 2018, 554(7693):544-548.
[cited by applicant]
Nagarajan et al., “Glycolipid-anchored IL-12 expressed on tumor cell surface induces antitumor immune response,” Cancer Research, May 15, 2002, 62(10):2869-2874.
[cited by applicant]
Naik et al., “Intravenous and isolated limb perfusion delivery of wild type and a tumor-selective replicating mutant vaccinia virus in nonhuman primates,” Hum. Gene Therapy, Jan. 2006, 17(1):31-45.
[cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2020/061578, mailed on Jun. 2, 2022, 8 pages.
[cited by applicant]
PCT International Search Report and Written Opinion in International Appln. No. PCT/US2020/061578, mailed on Mar. 22, 2021, 11 pages.
[cited by applicant]
Pearl et al., “Oncolytic Virus-Based Cytokine Expression to Improve Immune Activity in Brain and Solid Tumors,” Mol. Ther. Oncolytics, Mar. 20, 2019, 13:14-21.
[cited by applicant]
Pelin et al., “Abstract #PR19: Utilizing novel oncolytic vaccinia virus for selective expression of immunotherapeutic payloads in metastatic tumors,” Cancer Immunol. Res., Apr. 2020, 8(4_supplement):PR19.
[cited by applicant]
Ribas, “Adaptive Immune Resistance: How Cancer Protects from Immune Attack,” Cancer Discovery, Sep. 2015, 5(9):915-919.
[cited by applicant]
Sharma et al., “Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy,” Cell, Feb. 9, 2017, 168(4):707-723.
[cited by applicant]
Smith et al., “PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma,” Clin. Cancer Research, Jun. 1, 2019, 25(11):3443-3454.
[cited by applicant]
Sun et al., “Regulation and Function of the PD-L1 Checkpoint,” Immunity, Mar. 20, 2018, 48(3):434-452.
[cited by applicant]
Topalian et al., “Safety, activity, and immune correlates of anti-PD-1 antibody in cancer,” N. Engl. J. Medicine, Jun. 28, 2012, 366(26): 2443-2454.
[cited by applicant]
Tugues et al., “New insights into IL-12-mediated tumor suppression,” Cell Death Differentiation, Feb. 2015, 22(2):237-246.
[cited by applicant]
Twumasi-Boateng et al., “Oncolytic viruses as engineering platforms for combination immunotherapy,” Nat. Rev. Cancer, Jul. 2018, 18(7):419-432.
[cited by applicant]
Van der Woude et al., “Migrating into the Tumor: a Roadmap for T Cells, ” Trends Cancer, Nov. 2017, 3(11):797-808.
[cited by applicant]
Wang et al., “Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent,” Nat. Communications, Nov. 9, 2017, 8:1395, 15 pages.
[cited by applicant]
Yadav et al., “Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing,” Nature, Nov. 26, 2014, 515:572-576.
[cited by applicant]
Zamarin et al., “Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity,” Nat. Communications, Feb. 13, 2017, 8:14340, 14 pages.
[cited by applicant]
Zamarin et al., “Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy,” Sci. Transl. Medicine, Mar. 5, 2014, 6(226):226ra232, 12 pages.
[cited by applicant]
Zhang et al., “Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma,” Clin. Cancer Research, May 15, 2015, 21(10):2278-2288.
[cited by applicant]
Zou et al., “PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations,” Sci. Transl. Medicine, Mar. 2, 2016, 8(328):328rv324.
[cited by applicant]
U.S. Appl. No. 17/778,463, filed May 20, 2022, David Bartlett.
[cited by applicant]
Kobayashi et al., “FOXP3+ regulatory T cells and tumoral indoleamine 2,3-dioxygenase expression predicts the carcinogenesis of intraductal papillary mucinous neoplasms of the pancreas,” Pancreatology, 2010, 10(5):631-64…
[cited by applicant]
Nomi et al., “Clinical Significance and Therapeutic Potential of the Programmed Death-1 Ligand/Programmed Death-1 Pathway in Human Pancreatic Cancer,” Clin. Cancer Res., Apr. 2007, 13(7):2151-2157.
[cited by applicant]
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